Young-onset Chronic Kidney Disease with Biopsy-proven Chronic Tubulointerstitial Nephritis and a Rare REN Variant, with Coincident Drug-related Erythrocytosis: A Case Report

Abstract

Chronic Kidney Disease (CKD) in a young adult with a bland urinary sediment should prompt consideration of a monogenic tubulointerstitial disorder. Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD) is an under-recognised genetic cause, and in ADTKD due to REN the phenotype depends on where the variant lies in preprorenin. This report describes a 23-year-old man with six months of frothy urine who had young-onset CKD (estimated glomerular filtration rate 47-54 mL/min/1.73 m²) with sub-nephrotic proteinuria, hyperuricaemia and a negative immunological screen. He also had absolute erythrocytosis (haemoglobin 20.1 g/dL, packed-cell volume 60.1%) that was JAK2 V617F- and exon-12-negative with a normal erythropoietin and normal oxygen saturation, attributed to prior anabolic-androgenic (“testosterone-boosting”) agents and resolving after a single therapeutic venesection and cessation. Renal biopsy showed chronic tubulointerstitial nephritis with negative immunofluorescence, and whole-exome sequencing identified a heterozygous REN variant, c.708A>T (p.Gln236His), in the mature-renin domain - a region associated with later onset and absence of the anaemia that characterises signal-peptide variants. The variant is currently of uncertain significance and family segregation is advised. The case illustrates genotype-phenotype nuance in ADTKD-REN and the value of separating two coincident haematological and renal processes.